title: Chlamydia pneumoniae induces expression of pro-atherogenic factors through activation of the lectin-like oxidized LDL receptor-1.
abstract: Several lines of evidence have associated Chlamydia pneumoniae with cardiovascular disease including acceleration of atherosclerotic lesion progression in hyperlipidemic animal models by infection. Many of the pro-atherogenic effects of oxidized low-density lipoprotein (ox-LDL) occur through the activation of the lectin-like ox-LDL receptor-1 (LOX-1). Chlamydia pneumoniae upregulates the expression of the LOX-1 mRNA, promotes the uptake of ox-LDL, and utilizes the LOX-1 receptor for infectivity. The overall goal of this study was to determine whether C. pneumoniae organisms upregulated LOX-1 protein expression in vascular cells and whether upregulation of pro-atherogenic factors by C. pneumoniae occurred through LOX-1. Chlamydia pneumoniae induced LOX-1 protein expression in both endothelial cells and RAW macrophages. Upregulation was prevented by preincubation of cells with LOX-1 antibody prior to infection. Similarly, C. pneumoniae upregulated protein expression of adhesion molecules, MMP-1, and MMP-3, which was mitigated by anti-LOX-1 antibody. Prior treatment of organisms with PNGase, which removes the chlamydial glycan that is N-linked to the major outer membrane, abolished C. pneumoniae upregulation of LOX-1. These studies suggest that activation of LOX-1 expression occurs through binding of the chlamydial glycan and provides one mechanism by which C. pneumoniae infection could play a role in the pathogenesis of atherosclerosis.
authors.affiliation: Department of Epidemiology, University of Washington, Seattle, WA, USA lacamp@u.washington.edu.
authors.forename: Lee A
authors.initials: LA
authors.lastname: Campbell
authors.affiliation: Department of Epidemiology, University of Washington, Seattle, WA, USA.
authors.forename: Amy W
authors.initials: AW
authors.lastname: Lee
authors.affiliation: Department of Pathology, University of Washington, Seattle, WA, USA.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Rosenfeld
authors.affiliation: Department of Epidemiology, University of Washington, Seattle, WA, USA.
authors.forename: Cho-Chou
authors.initials: CC
authors.lastname: Kuo
mesh_terms: D000818:Animals; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism; D002478:Cells, Cultured; D016993:Chlamydophila pneumoniae / Q000472:pathogenicity*; D042783:Endothelial Cells / Q000382:microbiology / Q000502:physiology; D020869:Gene Expression Profiling; D054884:Host-Pathogen Interactions; D008264:Macrophages / Q000382:microbiology / Q000502:physiology; D020781:Matrix Metalloproteinase 1 / Q000096:biosynthesis; D019278:Matrix Metalloproteinase 3 / Q000096:biosynthesis; D051379:Mice; D011134:Polysaccharides / Q000378:metabolism; D051127:Scavenger Receptors, Class E / Q000096:biosynthesis*; D015854:Up-Regulation
chemical_list: D001425:Bacterial Outer Membrane Proteins; C495137:OLR1 protein, human; D011134:Polysaccharides; D051127:Scavenger Receptors, Class E; D019278:Matrix Metalloproteinase 3; D020781:Matrix Metalloproteinase 1
keywords: Chlamydia; LOX-1 receptor; adhesion molecules; atherosclerosis; glycan